Project Abstract: Acute HIV infection (AHI) is a crucially important, although currently neglected topic in public health, medical, and research ethics. Defined as the first few weeks or months following viral acquisition, AHI is a time of sharply heightened infectiousness, during which diagnosed patients must navigate difficult life decisions related to their physical and psychological well-being, as well as that of their partners and families. For many, this is a tumultuous period marked by incapacitating illness (acute retroviral syndrome), substance abuse, depression, guilt, anger, blame, and uncertainty. However, despite being a period of heightened vulnerability, AHI remains a key time-point at which interventions to prevent HIV transmission might be most effective, especially within hard to reach communities. In addition to HIV prevention, individuals diagnosed so early are of increasing interest to HIV researchers working to improve treatment or to find a cure. Currently, one of the greatest challenges to curing HIV is the persistence of latent viral reservoirs within the body. Individuals diagnosed and virally suppressed during AHI are generally provided long-term immunological benefits and tend to have smaller viral reservoirs. AHI diagnosed and treated patients may therefore be among the first to be eventually cured of HIV. For now, they represent a rare and valuable research population for studies seeking to prevent, eradicate, or permanently suppress HIV reservoirs. However, despite AHI's widely recognized scientific importance, to date few efforts have been made to understand what it like to live through AHI, or how these individuals experience clinical research participation. Understanding how acutely infected individuals' experiences affect clinical research participation, as well as how their experiences might differ from other research participants living with chronic HIV infection, is therefore essential to improving recruitment, consent, and retention practices among AHI diagnosed individuals as well as to ensuring the responsible conduct of research with similarly vulnerable research populations. This grant proposes to apply an innovative, ethnographic approach to clinical research in order to gain a deeper, nuanced understanding of AHI and its ethical dimensions. This project logically extends from our NIAID R01 (1R01A108366-01) study focused on the more general social and ethical implications of curing HIV. The goal of this study is to inform and enhance ethical conduct with this vulnerable research population. To this end, we propose three specific aims: (1) Examine the experiences of acutely infected research participants involved in HIV treatment and cure-related studies using anthropological methods; (2) Compare perceptions of risks and benefits of clinical HIV trial participation between acutely and chronically infected HIV research subjects; (3) Develop a set of ethical recommendations that address specific challenges related to identifying, recruiting, and retaining AHI individuals in HIV clinical (especially cure) research. Previously developed strong working relationships with local UNC and Duke acute HIV clinical research teams greatly increase our likelihood of success.